Polychlorinated biphenyl congener 180 (PCB 180) regulates mitotic clonal expansion and enhances adipogenesis through modulation of C/EBPβ SUMOylation in preadipocytes

• DOI: 10.1016/j.fct.2021.112205
• Publication Date: 2021-04-15T04:11:49Z
• Authors: Caixia Yu; Qing Wen; Qidong Ren; Yuguo Du; Xinni Xie
• Keywords: 0301 basic medicine; 0303 health sciences; Adipogenesis; CCAAT-Enhancer-Binding Protein-beta; Cell Cycle; Ubiquitination; Sumoylation; Cell Differentiation; Polychlorinated Biphenyls; Cysteine Endopeptidases; Mice; 03 medical and health sciences; 3T3-L1 Cells; Adipocytes; Animals; Humans

PCB 180 is a typical non-dioxin-like polychlorinated biphenyl (NDL-PCB). It is one of the most prevalent PCB-congeners found in human adipose tissue. However, the role of PCB 180 in obesity remains poorly understood. The aim of this study was to explore the adipogenic effect and mechanism of PCB 180. Significant enhancement in adipogenesis was observed when differentiating murine 3T3-L1 preadipocytes or human preadipocytes-visceral (HPA-v) that were exposed to PCB 180. Furthermore, exposure to PCB 180 during the first two days was critical to the adipogenic effect. According to results from sequential cell cycle analyses, cell counting, BrdU incorporation, and cyclin D1, cyclin B1, and p27 protein quantification, PCB 180 was found to enhance mitotic clonal expansion (MCE) during early adipogenic differentiation. Molecular mechanistic investigation revealed that PCB 180 promoted accumulation of the C/EBPβ protein, a key regulator that controls MCE. Finally, it was found that PCB 180 mitigated degradation of the C/EBPβ protein by repressing the SUMOylation and subsequent ubiquitination of C/EBPβ by the upregulation of SENP2. In summary, it was shown for the first time that PCB 180 facilitated adipogenesis by alleviating C/EBPβ protein SUMOylation. This result provides novel evidence regarding obesogenic effect of PCB 180.